In vitro and in vivo comparison of microcontainers and microspheres for oral drug delivery
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In vitro and in vivo comparison of microcontainers and microspheres for oral drug delivery. / Christfort, Juliane Fjelrad; Strindberg, Sophie; Al-khalili, Shaimaa; Bar-Shalom, Daniel; Boisen, Anja; Nielsen, Line Hagner; Mullertz, Anette.
I: International Journal of Pharmaceutics, Bind 600, 120516, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - In vitro and in vivo comparison of microcontainers and microspheres for oral drug delivery
AU - Christfort, Juliane Fjelrad
AU - Strindberg, Sophie
AU - Al-khalili, Shaimaa
AU - Bar-Shalom, Daniel
AU - Boisen, Anja
AU - Nielsen, Line Hagner
AU - Mullertz, Anette
PY - 2021
Y1 - 2021
N2 - Microcontainers, which are microfabricated cylindrical devices with a reservoir function, have shown promise as an oral drug delivery system for small molecular drug compounds. However, they have never been evaluated against a relevant control formulation. In the current study, we prepared microcrystalline cellulose (MCC) microspheres as a control for in vitro and in vivo testing of SU-8 microcontainers as an oral drug delivery system. Both dosage forms were loaded with paracetamol and coated with chitosan or polyethylene glycol (PEG) (12 kDa). These coatings were followed by an additional enteric coating of Eudragit (R) S100. In addition, a control dosage form was coated with Eudragit (R) alone. The dosage forms were evaluated in vitro, in a physiologically relevant two-step model simulating rat gastrointestinal fluids, and in vivo by oral administration to rats. In vitro, the microcontainers coated with PEG/Eudragit (R) resulted in a prolonged release of paracetamol compared to the respective microspheres, which was consistent with in vivo observations of a later time (T-max) for maximum plasma concentration (C-max) for the microcontainers. For microspheres and microcontainers coated with chitosan/Eudragit (R), the time for complete in vitro release of paracetamol was very similar, due to an earlier release from the microcontainers. This trend was supported by very similar T-max values in vivo. The in vitro in vivo relation was confirmed by a linear regression with R-2 = 0.9, when T-max for each dosage form was plotted as a function of time for 90% paracetamol release in vitro. From the in vivo study, the average plasma concentration of paracetamol 120 min after dosing was significantly higher for microcontainers than for microspheres (0.3 +/- 0.1 mu g/mL and 0.1 +/-
AB - Microcontainers, which are microfabricated cylindrical devices with a reservoir function, have shown promise as an oral drug delivery system for small molecular drug compounds. However, they have never been evaluated against a relevant control formulation. In the current study, we prepared microcrystalline cellulose (MCC) microspheres as a control for in vitro and in vivo testing of SU-8 microcontainers as an oral drug delivery system. Both dosage forms were loaded with paracetamol and coated with chitosan or polyethylene glycol (PEG) (12 kDa). These coatings were followed by an additional enteric coating of Eudragit (R) S100. In addition, a control dosage form was coated with Eudragit (R) alone. The dosage forms were evaluated in vitro, in a physiologically relevant two-step model simulating rat gastrointestinal fluids, and in vivo by oral administration to rats. In vitro, the microcontainers coated with PEG/Eudragit (R) resulted in a prolonged release of paracetamol compared to the respective microspheres, which was consistent with in vivo observations of a later time (T-max) for maximum plasma concentration (C-max) for the microcontainers. For microspheres and microcontainers coated with chitosan/Eudragit (R), the time for complete in vitro release of paracetamol was very similar, due to an earlier release from the microcontainers. This trend was supported by very similar T-max values in vivo. The in vitro in vivo relation was confirmed by a linear regression with R-2 = 0.9, when T-max for each dosage form was plotted as a function of time for 90% paracetamol release in vitro. From the in vivo study, the average plasma concentration of paracetamol 120 min after dosing was significantly higher for microcontainers than for microspheres (0.3 +/- 0.1 mu g/mL and 0.1 +/-
KW - Microdevices
KW - In vitro in vivo relation
KW - Paracetamol
KW - Eudragit (R) S100
KW - Chitosan
KW - PEG
KW - Mucoadhesive coatings
KW - POLYMERIC MICROCONTAINERS
KW - MICRODEVICES
KW - MUCOADHESIVE
KW - ABSORPTION
KW - CHITOSAN
KW - SYSTEMS
KW - BIOAVAILABILITY
KW - PERMEABILITY
KW - ENHANCEMENT
KW - RETENTION
U2 - 10.1016/j.ijpharm.2021.120516
DO - 10.1016/j.ijpharm.2021.120516
M3 - Journal article
C2 - 33775722
VL - 600
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 120516
ER -
ID: 272375194